An accurate and sensitive analysis suitable for routine use in the clinical laboratory is being developed and validated for the antipsychotic agent chlorpromazine (CPZ) thorazine R and its metabolites chlorpromazine sulfoxide (CPZSO), mono-N-desmethylchlorpromazine (Nor1CPZ), and di-N-desmethylchlorpromazine (Nor2CPZ) in human plasma using gas-liquid chromatography with a nitrogen-sensitive detector. The analysis is sufficiently sensitive to detect at least 5 ng/ml of CPZ, 20 ng/ml of CPZSO, 20 ng/ml of Nor1CPZ, and 10 ng/ml of Nor2CPZ in plasma. Plots of plasma standard concentration against gas chromatographic response (ratio of peak area of the compound to that of promazine added as the internal standard) are linear in the range studied (0 - 300 ng/ml) (r equals 0.99). No interfering compounds endogenous to plasma are encountered with this analysis. Assay precision, sample stability, and potential interference from other drugs and drug metabolites are currently under investigation. The method will be applied to both the plasma of patients who are receiving therapeutic doses of CPZ and to the plasma of patients who have ingested overdoses of CPZ in order to evaluate levels of the parent drug and its metabolites in these situations.